IL-17 Eliminates the Therapeutic Effects of Myelin Basic Protein-Induced Nasal Tolerance in Experimental Autoimmune Encephalomyelitis by Activating IL-6

Interleukin (IL)-17 is a proinflammatory cytokine primarily secreted by Th17 cells, which are a CD4⁺ T-cell subset. Th17 cells and IL-17 are important in the pathogenesis of multiple sclerosis and in its established animal model, experimental autoimmune encephalomyelitis (EAE). However, it is unclear whether IL-17 contributes to EAE immune tolerance. We used the myelin basic protein (MBP) peptide MBP 68–86 to induce nasal tolerance to EAE, and simultaneously interfered with the tolerance by treatment with different doses of IL-17. We found that IL-17 dramatically interfered with MBP 68–86-induced immune tolerance. IL-17 administration increased IL-6 release, skewing T cell differentiation towards Th17 cells and decreasing the number of Treg cells. This led to an imbalance between Treg cells and Th17 cells and spurred the development of EAE.     

Two novel mutations in the EPM2A gene in a Korean patient with Lafora's progressive myoclonus epilepsy

The progressive myoclonus epilepsy of the Lafora type (LD; MIM 254780) is a rare autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration, and the presence of periodic acid-Schiff-positive polyglucosan inclusions (Lafora bodies). Mutations in the EPM2A gene have recently been found to cause LD and about 30 or more mutations have been reported thus far. LD is relatively common in countries of the Mediterranean Basin, the Middle East, India, and Pakistan. Although a few sporadic cases with the typical LD phenotype have also been reported in the Far East including Korea and Japan, a recent effort to find mutations in Japanese LD families was not successful. In the present study, we report two novel mutations in a Korean girl with LD; a 1-bp insertion mutation (c.223insC; G75fsX107) in exon 1 and a missense mutation (c.559A>G; T187A) in exon 3 of the EPM2A gene. To our knowledge, this is the first report of a genetically confirmed case of LD in Koreans and also in the Far East.     

Mutagenic activity from nitrosation of oligoamines

To determine structural features necessary for the production of direct mutagenic activity from oligoamine-nitrate reaction mixtures, we systematically tested a group of aliphatic amine substrates for comutagenic action with nitrite. The ability to react with nitrite and form direct-acting mutagenic derivatives was common to a reasonably well defined class of aliphatic polyamines. In general, primary-secondary diamino compounds were mutagenic in the Ames Salmonella tester system when reacted with nitrite, whereas primary and secondary amines produced no direct mutagenic activity when tested separately. In combination with teritary amino groups, primary amines were inactive; one secondary-tertiary amine was tested, and this substrate produced mutagenic activity.     

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg⁻¹∙d⁻¹ had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg⁻¹∙d⁻¹. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.     

Pseudotumor appearance in chronic hepatitis

A pseudotumor appearance of the liver has not been previously described in chronic hepatitis. We reviewed 81 charts with a biopsy diagnosis of "chronic hepatitis" and at least one radiologic liver scan, and found four cases with a pseudotumor appearance. They all had features on radiologic scans suggestive of space-occupying lesions. Histology showed chronic hepatitis in all four. Two were cirrhotic, one due to alcohol and the other due to hepatitis B. The other two patients had chronic active hepatitis with regenerative nodules but only limited fibrosis, one due to hepatitis B, the other probable non-A, non-B. None had any evidence of hepatic malignancy. We conclude that some patients with chronic hepatitis may present with a pseudotumor appearance on radiological scans, due to the presence of regenerative nodules. Space-occupying lesions on liver scans in chronic hepatitis may represent non-neoplastic liver disease.     

The role of mtDNA deletion in the sensitivity to aminoglycoside antibiotic induced deafness]

OBJECTIVE: To establish an animal model of mitochondrial DNA (mtDNA) deletion and investigate the possible role of mtDNA deletion in aminoglycoside antibiotic induced deafness. METHODS: Thirty wistar rats (4 months) were randomly divided into group A and B. Doxorubicin (DOX) was subcutaneously injected at doses of 2 mg/kg twice per week for 3 months in group A and then kanamycin (KM) was intraperitoneally injected 500 mg/kg per day for 10 consecutive days. The treatments of group B were identical to group A, except normal saline was substituted for DOX. The thresholds of auditory brainstem response (ABR) were measured before and after the drug administrations. The inner ear membranous labyrinthine tissue was harvested and mtDNA was amplified to identify 4,834 bp deletion by PCR technique. RESULTS: The elevation of the mean ABR thresholds in group A(67.08 +/- 8.59) dB peSPL was significantly higher than that in group B (12.71 +/- 4.42) dB peSPL after KM administration (P < 0.001). In group A, 9 of the 15 rats demonstrated 4,834 bp mtDNA deletion. However, mtDNA 4,834 bp deletion was negative in group B animals. CONCLUSION: DOX can induce mtDNA deletion in the inner ear tissue of the rat. mtDNA deletion in the inner ear may play an important role in the hypersensitivity to aminoglycoside antibiotic ototoxicity.     

退变性腰椎管狭窄症手术治疗的探讨

目的：探讨退变性腰椎管狭窄症的手术治疗。方法：对９４例６０岁以上患者进行分型和手术治疗。结果：将本病分为Ⅰ型（侧隐窝狭窄型）;Ⅱ型（中央管狭窄型）;Ⅲ型（混合型）。对Ⅰ型手术方式采用单侧或双侧椎板开窗,扩大神经根管或（和）摘除髓核;对Ⅱ型行半椎板或全椎板切除术;对Ⅲ型行全椎板切除术。结论：通过术后疗效观察和３年随访,根据分型的不同选择不同的手术方式,可达到较好的临床疗效     

A claims data approach to defining an episode of care.

OBJECTIVE: To utilize health services research techniques in developing an episode of care using an administrative data set. This method is demonstrated for an episodic clinical condition, migraine. DATA SOURCES: Medicaid administrative data set of 3,372 patients with a diagnosis of migraine (ICD-9-CM 346.0, 346.1) in the state of Pennsylvania between May 1990 and March 1992. STUDY DESIGN: The duration of a migraine episode was measured by assessing the magnitude of resource utilization and the proportion of patients with charges in the period after the index migraine as compared to the period before the index migraine. A confidence interval (CI) was developed around each measure using bootstrap techniques. DATA COLLECTION METHODS: All charge data were extracted daily for a 113-day observation period surrounding each index migraine in order to observe the duration of impact of a migraine diagnosis on resource utilization. PRINCIPAL FINDINGS: The lower limits of both the 95% and 99% CIs for the difference in charges are greater than 0 for three weeks. The lower limits of both CIs for the difference in the proportion of patients with charges are above 0 for six weeks. CONCLUSIONS: Our analysis demonstrates that a health services research framework can be used to define an episode of care for a chronic disease category such as migraine. This method can be used to evaluate episodes of care for clinical studies of limited or episodic conditions and to complement clinical expertise in developing time horizons for clinical trials.